Impact of Epidermal Growth Factor Receptor (EGFR) Cell Surface Expression Levels on Effector Mechanisms of EGFR Antibodies

摘要: The epidermal growth factor receptor (EGFR) is a widely expressed Ag that successfully targeted in tumor patients by mAbs or tyrosine kinase inhibitors. A clinical study non-small cell lung cancer demonstrated positive correlation between EGFR expression levels and the therapeutic efficacy of mAb cetuximab. However, impact on different mechanisms action (MoAs) triggered has not been defined. In this study, BHK-21 cells were stably transfected to express levels, which quantified immunofluorescence immunohistochemistry compared with samples. These used systematically investigate target Fab- Fc-mediated MoAs mAb. negative potency Fab-mediated MoA was observed. Interestingly, Ab-dependent cell-mediated cytotoxicity (ADCC) NK cells, monocytes, polymorphonuclear as well complement-dependent positively correlated number molecules. comparison ADCC mononuclear required higher concentrations trigger significant killing. This confirmed an independent panel human lines carrying diverse genetic alterations. Furthermore, RNA interference-induced knockdown experiments reinforced killing conclusion, these results suggest may determine distinct patterns contribute